The autism spectrum disorders (ASDs) comprise a set of neurodevelopmental disorders that are, at best, still poorly understood and, yet, they are the fastest growing developmental disorder in the United States. Analysis of the post-mortem brain has provided some of the most valuable data for advancing our understanding of ASD pathophysiology. In addition, neural stem cells (NSCs) can be harvested from the post- mortem ASD brain, providing a critical tool for the study of ASDs, as detailed examination of the proliferation and differentiation of NSCs derived from ASD brains, compared with those derived from normal brains, is likely to yield important data regarding the etiology of the disease and provide new avenues for therapeutic approaches. The procurement of post-mortem ASD brains, however, has proven to be difficult. Thus, the generation of sufficient numbers of ASD NSC lines has been slow. Recent advances in stem cell research now allow for this difficulty to be overcome. It is now possible to de-differentiate or re-program human fibroblasts to an induced pluripotent stem cell (iPSC) state; that is, a line of stem cells that can differentiate into virtually any tissue cell type, such as brain, can be created from a fibroblast cell. This raises the potential of applying this technology to fibroblasts derived from ASD patients to allow study of resulting NSCs. Since fibroblasts are readily procured, sufficient statistical power for a whole host of studies can be achieved. We will apply the reprogramming technique to both fibroblasts derived from well- characterized patients with autism as well as those derived from normal individuals. Using the recently described gene candidates for reprogramming cells, we will transduce fibroblasts using published methods and characterize their conversion to iPSCs. We will use existing cell lines or cells lines recruited with our collaborators, procured under our stem cell-specific consent, for both the re-programming methodology and the compare and contrast evaluation of resulting cell lines. Specific methodology evaluation will be accomplished using fibroblasts and NSCs, already in our repository, that were derived from the same patients. The implication for the study of the ASDs simply cannot be overstated. Efficient generation of autism NSC lines will allow for studies that have never before been possible. These include (1) studies examining the detailed pathophysiology of the autism neuron, (2) studies of sufficient statistical power that can compare and contrast the effects of autism on neuronal differentiation, and (3) studies of the influence of environmental factors on these processes. Importantly, all data generated will be made available. The lines themselves will also be made available to the scientific community through our existing stem cell repository. This will leverage our efforts for maximal benefit to patients and families affected by autism.